The biology and growth of tumors in experimental animals will be investigated. The response of these in vivo tumor systems to established and potential antitumor drugs will be related to various aspects of tumor biology such as dissemination, metastasis, and tumor angiogenesis. Emphasis will be placed on developing solid tumor systems which will be useful in primary screening and detailed evaluation of drugs of potential value in clinical chemotherapy. The relationship of chemical structure to antitumor activity among major classes of natural products with antineoplastic activity will be studied both in vivo and in cell culture utilizing sensitive tumor systems and tumor sublines with acquired resistance to antitumor agents. Further emphasis will be placed on detailed evaluation of combinations of clinically active drugs with respect to the determination of optimal sequencing and scheduling of drugs. The mechanism of drug action as it relates to the cell division cycle and cytotoxicity will be investigated with emphasis on drugs which have antitumor activity yet are not myelosuppressive.